Psychopharmacology Khalid Bazaid, MB BS, FRCPC Assistant Professor Child & Adolescent Psychiatrist Department of Psychiatry College of Medicine King Saud University 4/22/2017 JES-2003 1

Outlines The role of psychotropic in the mental health and its therapeutic indications Identify specific cautions to be aware of the various psychotropic medications Discuss the adherence to medication treatment Psychotropic Medications Classifications Discuss the functions of the brain and the way this can be altered by the use of psychotropic medications Introduce you to the role of psychotropic in the mental health and its therapeutic indications Discuss how the neurotransmitters are affected by various psychotropic medications Identify specific cautions to be aware of the various psychotropic medications 4/22/2017 JES-2003 2

Psychopharmacology The aim is learn how to choose a psychotropic drug that is more: Effective Less toxic Better-tolerated The most targeted therapeutic agents 4/22/2017

Psychotropic Drugs Focus of all mental activity is the CNS (brain) Origin of psychiatric illness caused by many factors: Genetics Neurodevelopment factors Endocrinologic e.g. Hypothyroidism Autoimmune system (infections) Drugs Psychosocial experiences, stressors … etc. To date …Theories behind use of psychotropic drugs focuses on neurotransmitters and their receptors Psychotropic drugs act by modulating neurotransmitters 4/22/2017 4

Use of psychotropic medications Relieve or reduce symptoms/signs of dysfunctional thoughts, moods, or actions of mental illness Improve client’s functioning Increase compliance to other therapies Relieve or reduce symptoms/signs of dysfunctional thoughts, moods, or actions of mental illness and/or caused its impact 4/22/2017 5

Therapeutic Effects of Psychotropic Medications Do not “cure” Relieve or decrease symptoms Prevent or delay return of S/S Cannot be used as the sole treatment for disorders Need informed consent before starting Are broad spectrum and have effects on a large number of S/S Initial effects are sedative in nature May take weeks for effects to be seen 4/22/2017

Reasons for Non- adherence: Medications are expensive Unpleasant side effects Feel better and decide no longer need Stigma associated with having a mental illness and taking medications Paranoia or fears about medication usage particularly addition 4/22/2017 7

Encouraging Compliance to Medication Regimen Follow-up appointments With client to verify that client understands: the purpose, proper administration, intended effects, side and toxic effects of, and how to treat problems associated with medications Appropriate lab tests must be conducted to prevent complications and assure correct levels of drugs Encourage clients to participate in medication groups Can use injections of antipsychotics which will last from 2-4 weeks if clients are non-compliant 4/22/2017

Efficacy of Psychotropics with Children & Elderly Use with great caution Start low and go slow for both elders and children Children are faster metabolizer whereas elders have decrease liver & renal function Risk of injuries and falls with elderly 4/22/2017 9

Client & Family Teaching Purpose of the meds and benefits, side effects and how to treat SE What S/S indicate a toxic effect, and how to treat, and whom to call. Specific instructions about how to take the medications 4/22/2017

Psychotropic Medications Classifications Antipsychotics (Neuroleptics) Mood Stabilizers Antidepressants Anxiolytics (antianxiety) Sedatives Hypnotics Psychostimulants Antihistamines, antimuscarinics, dopamine agonists 4/22/2017 11

Psychotropic Medications Classifications … continued In many instances, drugs have multiple indications: SSRIs (selective serotonin reuptake inhibitors) are both antidepressants and anxiolytics. SDAs (serotonin-dopamine antagonists) are both antipsychotics and mood stabilizers. Psychotropic drugs have also been organized according to structure (e.g. Tricyclic). mechanism (e.g. monoamine oxidase inhibitor [MAOI])

Antipsychotics Schizophrenia Disorders Bipolar disorder Major Depression with psychotic features Tourette’s Syndrome Delirium, Dementia, and Delusions Control of intractable hiccups Aggressive behavior 4/22/2017 13

Antipsychotic - Neuroleptics First generation Post synaptic D2 receptor. Dopamine receptor antagonists (DRAs) Low potency: hypotension, sedation, weight gain more anticholinergic less antidopamenergic less EPS. e.g. Mellaril, chlorpromazine High potency: More antidopamenergic more EPS less anticholinergic e.g. Haldol Atypical Antipsychotics (2nd and 3rd generation) D2, D4, 5HT2 Serotonin dopamine antagonists (SDAs) Alpha adrenergic, muscarinic receptors e.g. Clozaril Risperdal Zyprexa Seroquel Abilify Geodon Invega Zeldox

First Generation Antipsychotic Block predominantly dopamine activity High incidence of abnormal movements little effect on serotonin (Also blocks acetylcholine, norepinephrine to some degree) Blocks the H receptor for histamine results in sedation and weight gain 4/22/2017 15

Side Effects of 1st Gen Drugs-1 Dystonia (EPS) spasms of the eye, neck-torticollis, back, tongue-happens within 72 hrs ( reversible) Akathisia (EPS) restlessness Pseudoparkinson - S/S similar to Parkinson's-see in 1-2 weeks. May disappear. TX. With Cogentin Tardive Dyskinesia-bizarre facial and tongue movements (irreversible) 4/22/2017 16

Side Effects of 1st Gen Drugs-2 Blurred vision, dry mouth, constipation and urinary retention, tachycardia-anticholinergic S/E Sexual dysfunction Severe dysrhythmias Orthostatic hypotension Agranulocytosis In men can lead to gynecomastia Amenorrhea Galactorrhea photosensitivity & skin rashes Reduction is seizure threshold – Low potency 4/22/2017 17

Precautions and/or contraindicated When using 1st Gen Antipsychotics Blood dyscrasias Liver, renal, or cardiac insufficiency CNS depressants, including ETOH Tegretol in conjunction with antipsychotics causes up to 50% reduction in antipsychotic concentrations SSRI’s in conjunction with antipsychotics may cause sudden onset of EPS Don’t give if have: Parkinson's disease, prolactin dependent cancer of the breast Cigarette smoking causes reduced plasma concentrations of antipsychotics Antacids, activated charcoal can reduce the absorption of DRAs Faverin in conjunction with antipsychotics causes increased concentrations of Haldol and Clozaril Beta Blockers in conjunction with antipsychotics cause severe hypotension Antidepressants in conjunction with antipsychotics may cause increased plasma level of both 4/22/2017 18

First Generation Antipsychotic Medications Are useful in getting out of control behavior under control quickly. These can be given with lithium to get treat acute mania. Seroquel is effective in the maintenance treatment of Bipolar-Depressive phase 4/22/2017 19

Atypical Antipsychotics Action: Blocks dopamine receptors and to a lesser degree serotonin receptors, Also block receptors for norepinephrine , histamine, acetylcholine Nicer drugs and are used more Decrease positive and negative S/S of Schizophrenia Lower Incidence of abnormal movements Biggest S/E is weight gain e.g. Zyprexa 4/22/2017 20

Positive & Negative S/S of Schizophrenia Hallucinations Delusions Abnormal thoughts Bizarre behavior Confused thoughts Negative: Blunted affect Poverty of speech Social withdrawal Poor motivation 4/22/2017

Atypical Antipsychotics-2nd & 3rd generation: Clozaril (clozapine) low incidence of abnormal movements Most common S/E: Nausea, constipation, sedation, drowsiness, weight gain Other S/E are: hypersalivation, tachycardia, dizziness, seizure risk possible fatal side effect: bone marrow suppression & Agranulocytosis (rare) 4/22/2017 22

Atypical Antipsychotics-2nd & 3rd generation - 2 Risperidone Does not cause bone marrow suppression Can cause at higher doses movement disorders Available as a long acting injection Can be used to treat mania Seroquel (Quetiapine) S/E sedation, weight gain and headache Not associated with abnormal movements May cause AV block 4/22/2017 23

Atypical Antipsychotics-2nd & 3rd generation - 3 Zyprexa (Olanzapine) does not cause bone marrow suppression Can cause weight gain & hyperglycemia Drowsiness, dry mouth, constipation, and restlessness Geodon (Ziprasidone) Binds to multiple receptor sites Drowsiness, headache, GI upset Can prolong the QT interval-can be fatal if history of cardiac arrhythmias Abilify (Aripiprazole) Dopamine stabilizer Partial agonist at the D2 receptor In areas of the brain with excess dopamine, it lowers dopamine In areas of low dopamine, it stimulates receptors to raise the dopamine level Main S/E are headache, somnolence, agitation, anxiety, insomnia, and GI upset 4/22/2017 24

Antipsychotics-Long acting preparation Can be given be given as an IM injection (depot preparations) if have difficulty taking oral meds. Can use lower doses when given IM, so less risk of tardive dyskinesia 4/22/2017

Neuroleptic Malignant Syndrome Rare, but fatal complication from all antipsychotic drugs See more with 1st generation drugs Severe muscle rigidity High temperature Associated S/S: Tachycardia Hypertension Stupor Coma Abnormal labs including leukocytosis , Elevated Creatinine phosphokinase (CPK) & LFT 4/22/2017 26

Mood Stabilizers Used in the treatment of Manic (Bipolar) disorder, and in some forms of depression Drugs used: Lithium and Antiepileptic Drugs 4/22/2017 27

Lithium Mechanism of action unknown Alters electrical conductivity potential threat to all body functions that are regulated by electrical currents Can cause polyuria and polydipsa due to Na and K alterations Has the lowest therapeutic index of all psych drugs Have to monitor blood levels Interacts with Sodium and Potassium 4/22/2017 28

Lithium Maintenance blood levels of lithium are usually 0.4-1.3 mEq (toxicity occurs with levels > 1.5 mEq/L) Sign of toxicity is a fine intention tremor that becomes more pronounced and coarse Risk of thyroid & kidney disease If toxic S/S occur discontinue the drug and notify health care provider Lithium should be taken with food Client must eat a balanced diet with normal sodium intake and take in adequate fluid (about 2-3 liters/day). Excretion is via renal system Dehydration and salt restriction can increase lithium levels & cause toxicity. Takes 2-3 weeks for lithium to become effective (may use antipsychotic until therapeutic levels are reached) Therapeutic index From Wikipedia, the free encyclopedia Jump to: navigation, search This article needs additional citations for verification. Please help improve this article by adding reliable references. Unsourced material may be challenged and removed. (May 2010) The therapeutic index (also known as therapeutic ratio), is a comparison of the amount of a therapeutic agent that causes the therapeutic effect to the amount that causes death. Quantitatively, it is the ratio given by the lethal dose divided by the therapeutic dose. A therapeutic index is the lethal dose of a drug for 50% of the population (LD50) divided by the minimum effective dose for 50% of the population (ED50). A higher therapeutic index is preferable to a lower one: a patient would have to take a much higher dose of such a drug to reach the lethal threshold than the dose taken to elicit the therapeutic effect. Generally, a drug or other therapeutic agent with a narrow therapeutic range (i.e. having little difference between lethal and therapeutic doses) may have its dosage adjusted according to measurements of the actual blood levels achieved in the person taking it. This may be achieved through therapeutic drug monitoring (TDM) protocols. The therapeutic index for diazepam is somewhat forgiving at about 100. Other drugs, however, are much less so, such as Digoxin, with an index of 2 or 3. [1] Other examples of drugs with a narrow therapeutic range, which may require drug monitoring both to achieve therapeutic levels and to minimize toxicity, include: dimercaprol, theophylline, warfarin and lithium carbonate. Some antibiotics require monitoring to balance efficacy with minimizing adverse effects, including: gentamicin, vancomycin, amphotericin B, and polymyxin B. 4/22/2017 29

Signs & Symptoms of Lithium Toxicity Severe Toxicity: decrease level of consciousness to stupor and finally coma Seizures, severe hypotension, severe polyuria with dilute urine Fine hand tremors that progress into coarse tremors Mild GI upset progressing to persistent upset Slurred speech and muscle weakness progressing to mental confusion 4/22/2017

Lithium Lithium serum concentrations are increased by Flouxetine (Prozac), ACE inhibitors, Thiazide diuretics, and NSAIDs Lithium serum concentrations are decreased by theophylline, osmotic diuretics, and urine alkalinizers 4/22/2017

Contraindications for Lithium Renal disease Cardiac disease Severe dehydration Sodium depletion Brain damage Pregnancy or lactation Use with caution in the elderly or clients with diabetics, thyroid disorders, urinary retention, and seizures 4/22/2017

Anticonvulsants/Antiepileptic Drugs Causes an increase in GABA in the CNS-which causes a decrease in anxiety. Reduce the mood swings with bipolar 4/22/2017

Anticonvulsants/Antiepileptic Drugs Tegretol (carbamazepine)-also used to treat severe pain (i.e. trigeminal neuralgia), cause agranulocytosis and aplastic anemia Depakote (Valproic acid)-can cause hepatic failure, pancreatitis, & thrombocytopenia. Watch for liver failure Klonopin (Clonazepam) Lamictal (Lamotrigine)-can have a rare but fatal dermatological condition 4/22/2017 34

Toxic Effects of Anticonvulsants Tegretol can cause agranulocytosis and aplastic anemia Depakote can cause liver dysfunction, hepatic failure, and blood dyscrasias including thrombocytopenia Depakote interacts with drugs that are metabolized by the liver 4/22/2017

Contraindications for Anticonvulsants Hepatic or renal disease Pregnancy Lactation Presence of blood dyscrasias 4/22/2017

Psychoeducation when using anticonvulsants Monitor blood levels of mood stabilizers to prevent toxicity Monitor liver, renal function tests and CBCs Depakote must be swallowed whole, not cut, chewed, or crushed to prevent irritation 4/22/2017

Evolution of Antidepressant Drugs 1950 1960 1970 1980 1990 2000 2009 Phenelzine Phenelzine Imipramine Imipramine Maprotiline Maprotiline Fluoxetine Fluoxetine Nefazodone Escitalopram Valdoxan Isocarboxazide Isocarboxazid Clomipramine Clomipramine Amoxapine Amoxapine Sertraline Sertraline Mirtazapine Duloxetine Tranylcypromine Tranylcypromine Nortriptyline Nortriptyline Mianserine Paroxetine Reboxetine Trazodone Amitriptyline Amitriptyline Fluvoxamine Venlafaxine Citalopram Tianeptine Desipramine Desipramine Bupropion Milnacipran Moclobemide 38

Antidepressants Treatment of depressive moods, including bipolar disease 4 categories: Tricyclics (TCA) MAOI’s SSRI’S Atypical Antidepressants 4/22/2017 39

Antidepressant Drugs Tricyclics- Elavil, Tofranil SSRI’s- Lustral, Seroxat MAOI’s- Nardil, Parnate 4/22/2017

Atypical Antidepressants Inhibits reuptake of serotonin: Trazodone (desyrel) Norepinephrine Dopamine Reuptake Inhibitor (NDRI): Wellbutrin (Bupropion) Sertonin Norepinephrine Reuptake Inhibitor-(SNRI): Effexor (venlafaxine) Cymbalta (duloxetine) Increases release of serotonin & norepinephrine: Remeron (mirtazapine) 4/22/2017 41

Atypical Antidepressants Trazodone: alternative to TCA’s, may cause orthostatic hypotension, sedation, and priapism in males Remeron: causes sedation, weight gain, dry mouth, constipation Wellbutrin (zyban): rarely causes sedation, weight Gain, or sexual dysfunction Used for smoking cessation. Most common S/E are headaches, insomnia & nausea May lower seizure threshold 4/22/2017 42

Atypical Antidepressants: serotonin norepinephrine reuptake inhibitor (SNRI) Skipping 1 dose can cause withdrawal S/S Very effective in treating severe depression Cymbalta is effective in treating somatic symptoms e.g. pain SNRI-blocks uptake of serotonin and norepinephrine Drugs include Effexor & Cymbalta Good for clients with anxiety S/E:GI, sexual dysfunction, insomnia, agitation 4/22/2017 43

Major Indications for Antidepressants Major Depressive disorder Bipolar depression Anxiety disorders: Panic disorder Obsessive-Compulsive Phobic disorders PTSD Substance Abuse Chronic Pain Tourette’s Disorder ADHD Eating disorders Sleep disorders Migraines Enuresis 4/22/2017 44

TriCyclicAntidepressant (TCA): Tryptizol, Pamelor, Tofranil, Anafranil, Aventyl, Asendin, Sinequan Other side effects: Orthostatic hypotension Sedation Weight gain Confusion-esp. elderly Arrhythmias Blocks the reuptake of norepinephrine and serotonin Tricyclic drugs block the muscarine receptors causing anticholinergic side effects 4/22/2017 45

TCA’s Contraindications Do not mix with ETOH (none of the psych drugs should be mixed with ETOH) Dementia Suicidal clients Cardiac disease Pregnancy Seizure disorders Urinary retention Dose for elderly should be ½ of adult dose TCA’s and MAOIs are effective in treatment of depression are not as safe nor well tolerated as the newer antidepressants Toxic Effects: possibility of cardiac toxicity in overdose 4/22/2017

SSRI’s Prozac, Lustral, Seroxat, Faverin, Cipralex, Serzone Blocks the reuptake of serotonin into the neuron Are very safe and are not lethal in overdose Good choice with the elderly-very few side effects If used with MAOI’s may cause Serotonin Syndrome: seizure, death If used with TCA’s may cause TCA toxicity Takes 2 weeks to feel effects Side-effect: GI, CNS however the biggest is sexual dysfunction & weight gain Contraindication: Cardiac dysrhythmias 4/22/2017

MAOI’s Nardil, Parnate Inhibits MAO, thus interfering with breakdown of norepinephrine, dopamine, and serotonin Avoid foods with tyramine (aged cheese, red wine, beer, chocolate, etc.) MAOI’s don’t play well with other drugs!! Toxic effects: hypertensive crises 4/22/2017 48

Adverse effets linked with neurotransmitter activity and receptor binding Activating side effects 5-HT2 agonism Weight gain Ach antagonism Blurred vision Nausea 5-HT3 agonism Activating effects NE reuptake inhibition Postural hypotension Dizziness Reflex tachycardia α2 antagonism Priapism DA reuptake Psychomotor activation Traditional Antidepressants 5-HT reuptake H1 antagonism α1 antagonism Dry mouth Urinary retention Tremor-CV troubles Sexual dysfunction GI disturbances Sedation/ drowsiness Constipation Sinus tachyardia Memory dysfunction Psychosis - Abuse The “cleaner” the drug, the better the side effect profile. Agents that have greater affinities for multiple receptors will, by definition, run a greater risk of creating unwanted side effects. This slide shows the relationship between neurotransmitter affinity, receptor activity, and clinical side effects. Adapted from Richelson 1993

Antianxiety/Anxiolytic Drugs GABA exerts an inhibitory effect on neurons These drugs enhance its effect and produce a sedative effect Therefore reduce anxiety The most common used drugs here are the Benzodiazepines 4/22/2017 50

Benzodiazepines Valium, Xanax, Ativan , Librium, Lexotanil Dalmane, Halcion (used as sleep aides-short term) Used for anxiety disorders, ETOH withdrawal, muscle spasm, sedation, insomnia, and epileptics/seizures Risk of dependency Avoid ETOH Causes sedation-don’t drive!! 4/22/2017 51

Benzodiazepines Side Effects Toxic Effects Contraindications Teaching Drowsiness, confusion, sedation, and lethargy Toxic Effects Respiratory depression esp. with ETOH use! Contraindications Combination with other CNS depressants Renal or hepatic dysfunction (may use Ativan) History of drug abuse or addiction Depression and suicidal tendencies Teaching Use short term due to risk of drug dependency Avoid ETOH and other CNS depressants Can impair ability to drive Sudden D/C of benzodiazepines might cause withdrawal s/s 4/22/2017

Non-benzodiazepine Anxiolytic BuSpar (Buspirone) Reduces anxiety without strong sedative-hypnotic properties Not a CNS depressant Takes 2 weeks to feel effects No potential for addiction Side Effects Dizziness, dry mouth, nervousness, diarrhea, headache, excitement Toxic Effects Lethal dose is 160-550 times the daily recommended dose Contraindications Use with caution in PG women Nursing mothers Clients with renal or hepatic disease Anyone taking MAOs 4/22/2017 53

Sedative/Hypnotic Drugs Anxiolytic and hypnotic Can lead to tolerance and dependency Use for short term Drugs used benzodiazepines: Dalmane, Restoril, Halcion Non-benzodiazepines: Ambien, Sonata, Lunestra 4/22/2017 54

Psychoeducation when using Benzodiazepine Teaching Use short term(1-2 weeks) Carefully need to taper these off-never stop cold turkey Do not take with other meds without talking to provider first Do not drive if sedated on these!! 4/22/2017

Client Teaching for Non-benzodiazepines Long term use not recommended Do not drive when taking Can repeat Sonata up to 4 hours before arising 4/22/2017

ADD/ADHD-Psychostimulants S/E: wt. loss, anorexia, insomnia, headache, long-term growth suppression Potential for abuse Also used to treat narcolepsy Ritalin, Adderall, Dexedrine, Concerta, Daytrana Action= increasing the release and blocking the reuptake of monoamines (dopamine, norepinephrine) 4/22/2017 57

ADD/ADHD-Psychostimulants Intended effects: Increased attention span & concentration Decreased distractibility, hyperactivity, and impulsivity Treatment of ADHD, ADD, & narcolepsy S/E: Anorexia Wt. loss Growth retardation in children Insomnia Headache Cardiovascular effects-high blood pressure, dysrhythmias Contraindications: Hx of drug abuse & dependency, severe anxiety, anorexia, MAIOIs 4/22/2017

ADD/ADHD- Non-Stimulants Strattera (atomoxetine) Controls symptoms thru selective inhibition of norepinephrine Takes 1-3 weeks to feel effects No abuse potential and is not considered a controlled substance 4/22/2017 59

Meds used to Treat Extrapyramidal SE Cogentin Benadryl Artane Symmetrel Requip Akineton Kemadrin These meds should be taken simultaneously with antipsychotic meds to prevent EPS 4/22/2017 60

Herbal Medicines Ginkgo biloba-helps with memory Kava-Kava St. John’s Wart 4/22/2017

Questions after lecture? Please e-mail (kbazaid@ksu.edu.sa) or call (01 467 1717) Interested in learning more about child and adolescent psychiatry? Arrange to attend OPD Consider an elective rotation during internship or otherwise 4/22/2017 4/22/2017 62

Meds for Alzheimer’s Drugs here are used to slow the progression of the disease Memantine (Namenda, Ebixa) Cognex (tacrine) Aricept (donepezil) Exelon (Rivastigmine) Razadyne (galantamine) 4/22/2017 63

PET Scan=positron-emission tomography (PET) scans Useful in identifying physiological and biochemical changes as they occur in living tissue i.e. clients with schizophrenia PET scans show a decrease of glucose in the frontal lobes of unmedicated clients, also can indicate mood disorders, ADHD Radioactive substance is injected, travels to the brain, and illuminates the brain. Have 3D visualizations of the CNS 4/22/2017